The discovery of Helicobacter pylori (H. pylori) infection has greatly changed our understanding of upper G.I. tract diseases, including peptic ulcer disease and stomach cancer. Antibiotics are first-line treatment for ulcer patients which are infected with this bacterium. Also, the World Health Organization has classified H. pylori as a group I or definite carcinogen. People infected with H. pylori have a 3 to 6 fold higher risk of developing gastric cancer than non-infected persons. Progression from superficial gastritis caused by H. pylori to atrophic gastritis with intestinal metaplasia is felt to be a precursor to gastric cancer development. Investigators have postulated that the natural progression of H. pylori-associated chronic gastritis is to atrophic gastritis, which may be prolonged or shortened by dietary factors. A diet rich in fruits and vegetables and low in starch and salt is associated with a decreased risk of developing gastric cancer. The presence of antioxidants in this diet has been postulated to be responsible for t he decrease in cancer risk. We postulated that H. pylori increases the susceptibility of gastric cells to injury from reactive oxygen species, in part by generating the production of intracellular reactive oxygen species. The specific aims of this grant are (1) to determine the ability of H. pylori exposure (live bacteria vs. bacterial proteins) to induce oxidant related DNA damage in gastric epithelial cell lines; and elucidate the spectrum and repair course of oxidant related DNA adducts formed after exposure to H. pylori (live bacteria vs. bacterial proteins) using fluorescent microscopy, fluorometer and lucigenin- and luminol-derived chemiluminescence; and determine whether or not cytochrome p450s and/or mitochondria are important in the generation of reactive oxygen species after exposure to H. pylori. (3) Further evaluate the role of glutathione peroxidase and catalase in the detoxification of intracellular reactive oxygen species, and their association with oxidant induced DNA adducts and cell injury. These studies will demonstrate the potential significant role for bacterial in stimulating oxidative cell injury and DNA damage which may increase the susceptibility of lining epithelial cells to carcinogenic conversion. Relationship of this Project to the Overall Priorities and Objectives of the Partnership This project will help to achieve the overall goals and objectives of this partnership because it addresses a cancer which predominantly effects minorities in this country. Also, gastric cancer is caused in part by. H. pylori infection which is more prevalent in minorities. This project is also appropriate for this partnership because Howard University is interested in developing research in area of gastrointestinal cancers (gastric & colorectal cancer). This research project originates at Howard University and matches the expertise of Dr. Smoot in the area of H. pylori pathogenesis and that of Dr. Groopman in oxidative DNA damage, from environmental exposures. This collaboration will assist Dr. Smooth, who started this research with an R03 grant funded by the NCI, in developing this research into an R01 funded grant. There is currently one manuscript in press from this collaboration, which began in the fall of 199. This is appropriate from Johns Hopkins' perspective because the studies being conducted by Dr. Groopman will elucidate the spectrum of oxidant related DNA adducts and repair course cause by exposure to this bacteria which infects mostly minorities in this country. These studies are expected to lead to patient oriented research where one may be able to cancer assess in minorities by measuring oxidative DNA adducts in gastric tissue of persons currently or previously infected with this bacterium.